POS0514 BONE EROSION REMODELING AFTER DEPLETION OF MONOSODIUM URATE DEPOSITION WITH INTENSIVE URATE-LOWERING WITH PEGLOTICASE IN PATIENTS WITH UNCONTROLLED GOUT: MIRROR RCT DUAL-ENERGY CT FINDINGS
Authors: N. Dalbeth, J. Botson, K. Saag, A. Kumar, L. Padnick-Silver, B. Lamoreaux, F. Becce
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Monosodium urate (MSU) crystal deposits can be visualized and quantified with dual-energy CT (DECT) <sup>[1]</sup>, with DECT studies showing an association between MSU deposition and bone erosion <sup>[2]</sup>. Pegloticase rapidly lowers serum urate (SU) to near zero in uncontrolled gout patients (pts), with methotrexate (MTX) co-therapy recommended to increase SU lowering response rate (71% vs 39% with pegloticase+placebo [PBO]) and decrease infusion reaction risk (4% vs 31%; MIRROR RCT) <sup>[3]</sup>. MIRROR open-label trial (pegloticase+MTX co-therapy for ≤52 wks) DECT findings showed rapid, progressive MSU deposition volume (V<sub>MSU</sub>) reduction with subsequent bone erosion remodeling in the 2 imaged pts <sup>[4]</sup>. The MIRROR RCT trial had a larger number of pts who underwent serial DECT imaging during pegloticase+MTX/PBO co-therapy, the findings of which are reported here. <h3>Objectives</h3> To examine V<sub>MSU</sub> and bone erosion imaging findings of MIRROR RCT participants who underwent serial DECT imaging. <h3>Methods</h3> Pts were randomized 2:1 to receive oral MTX (15 mg/wk) or PBO as co-therapy to pegloticase (8 mg biweekly infusions). Serial images were obtained at DECT-capable sites using a standard acquisition protocol at prespecified time points during the 52-wk treatment period (Day 1 [first pegloticase infusion]; Wks 14, 24, 52). Bilateral hand/wrist, elbow, foot/ankle, and knee images were obtained. Images were post-processed using default settings and interpreted by an independent central reader blinded to treatment group and SU lowering response. V<sub>MSU</sub> was measured in each scan. Up to 3 of the largest bone erosions per imaged region were assessed for evidence of remodeling, defined as a decrease in size, recortication, and/or new bone formation. Erosion size was evaluated as the product of the largest longitudinal and axial slice dimensions. Pts with baseline and Wk 52 images were included in analyses, excluding imaged regions with a baseline V<sub>MSU</sub> &lt;0.5 cm<sup>3</sup> to prevent large contributions of potential DECT artifacts <sup>[5]</sup>. DECT-imaged regions were also radiographed and photographed. <h3>Results</h3> 6 pts receiving pegloticase+MTX co-therapy and 2 pts receiving pegloticase+PBO co-therapy were included in analyses. In the MTX group, 5 pts had SU &lt;6 mg/dL during Month 6 and received 52 wks of pegloticase+MTX co-therapy; 1 pt discontinued pegloticase+MTX at Wk 6 due to SU rise, continuing on allopurinol (mean SU on allopurinol = 4.6 mg/dL). In the PBO group, 1 pt had sustained SU-lowering through Month 6 and received 42 wks of pegloticase+PBO, continuing on febuxostat (mean SU on febuxostat = 5.2 mg/dL); 1 pt discontinued pegloticase+PBO at Wk 6 due to SU rise, continuing on allopurinol (mean SU on allopurinol = 3.0 mg/dL). V<sub>MSU</sub> markedly decreased during therapy in both treatment groups (Wk 52, MTX: -94% ±9% [9 imaging regions of 6 pts], PBO: -96% ±3% [4 imaging regions of 2 pts]). Evidence of concomitant bone erosion remodeling (<b>Figure 1</b>) was observed in 69% (29/42) of evaluated erosions (9/12 [75%] imaged regions; 6/8 [75%] pts). Of the 29 erosions with remodeling, 100% had a decrease in size (mean: -7% change at Wk 52), with recortication (4 erosions [14%]) and new bone formation (3 erosions [10%]) also observed in some erosions. <h3>Conclusion</h3> In agreement with a prior serial DECT study <sup>[4]</sup>, rapid and near complete V<sub>MSU</sub> depletion was observed within 1 year of initiating pegloticase therapy. Concomitant bone erosion remodeling was also observed after 52 wks of intensive urate-lowering therapy. In these limited cases, DECT findings were similar between treatment groups. It is likely that SU-lowering, not MTX use, resulted in DECT changes, but further study is needed. However, these analyses suggest that bone remodeling is possible following MSU crystal depletion. <h3>References</h3> [1]Choi HK et al. <i>Ann Rheum Dis</i> 2012, 71:1466-71 [2]Shi D et al. <i>Medicine (Baltimore</i>) 2019;98:e18431 [3]Botson et al. <i>Arthritis Rheumatol</i> 2022 [Epub ahead of print] [4]Dalbeth N et al. <i>Rheumatology (Oxford</i>) 2022;61:4898-904 [5]Coupal TM et al. <i>AJR Am J Roentgenol</i> 2016;206:119-28 <h3>Acknowledgements</h3> This study was funded by Horizon Therapeutics plc. <h3>Disclosure of Interests</h3> Nicola Dalbeth Speakers bureau: Arthrosi, AstraZeneca, Dyve Biosciences, Hikma, Horizon, JPI, JW Pharmaceutical Corporation, LG Chem, PK Med, PTC Therapeutics, Protalix, Selecta, Unlocked Labs, Consultant of: Arthrosi, AstraZeneca, Dyve Biosciences, Hikma, Horizon, JPI, JW Pharmaceutical Corporation, LG Chem, PK Med, PTC Therapeutics, Protalix, Selecta, Unlocked Labs, John Botson Speakers bureau: AbbVie, Amgen, Aurinia, Chemocentryx, Horizon, Lilly, Novartis, Consultant of: AbbVie, Amgen, Aurinia, Chemocentryx, Horizon, Lilly, Novartis, Grant/research support from: Horizon, Allena, Radius Health, Kenneth Saag Grant/research support from: Alinea, Horizon, Lg, Sobi, Ada Kumar Shareholder of: Horizon, Employee of: Horizon, Lissa Padnick-Silver Shareholder of: Horizon, Employee of: Horizon, Brian LaMoreaux Shareholder of: Horizon, Employee of: Horizon, Fabio Becce Consultant of: Horizon, Grant/research support from: Siemens Healthineers (DECT research agreement).